Summary paragraph/Abstract Immunologic responses during sepsis vary significantly among patients and evolve over the course of illness. Sepsis has a direct impact on the immune system due to adverse alteration of the production, maturation, function, and apoptosis of immune cells. Dysregulation in both the innate and adaptive immune responses during sepsis leads to a range of phenotypes consisting of both hyperinflammation and immunosuppression that can result in immunoparalysis. In this review, we discuss components of immune dysregulation in sepsis, biomarkers and functional immune assays to aid in immunophenotyping patients, and evolving immunomodulatory therapies. Important research gaps for the future include: 1) Defining how age, host factors including prior exposures, and genetics impact the trajectory of sepsis in children, 2) Developing tools for rapid assessment of immune function in sepsis, and 3) Assessing how evolving pediatric sepsis endotypes respond differently to immunomodulation. Although multiple promising immunomodulatory agents exist or are in development, access to rapid immunophenotyping will be needed to identify which children are most likely to benefit from which therapy. Advancements in the ability to perform multidimensional endotyping will be key to developing a personalized approach to children with sepsis.
The complex physiology and medical requirements of children with sepsis and multiple organ dysfunction syndrome (MODS) challenge traditional care coordination models. While the involvement of multiple clinical subspecialty services is often necessary to support different care processes and individual organ system dysfunctions, it can also delay the diagnostic process, monitoring, and treatment. The logistics of coordinating with many specialty providers for critically ill patients are challenging and time consuming, and often can result in fragmented communication. To address these and other related issues, we developed a new multi-disciplinary consult service focused on streamlining diagnostics, management, and communication for patients with sepsis and MODS-associated immune dysregulation. The service, called the Program in Inflammation, Immunity, and the Microbiome (PrIIMe), is now a hospital-wide clinical consult service at our institution caring for a broad group of patients with immune dysregulation, particularly focusing on patients with sepsis and MODS. In this paper, we summarize the development, structure, and function of the program, as well as the initial impact. This information may be helpful to clinicians and healthcare leaders who are developing multi-disciplinary consult services for children with complex care needs, especially those with sepsis and MODS-associated immune dysregulation. Impact The care of children with sepsis and multiple organ dysfunction-associated immune dysregulation requires rapid and flexible involvement of multiple clinical subspecialists that is difficult to achieve without fragmented care and delayed decision making. In this narrative review we describe the development, structure, and function of a multi-disciplinary consult service at a children’s hospital dedicated to helping coordinate management and provide continuity of care for patients with sepsis and multiple organ dysfunction-associated immune dysregulation. This information may be helpful to clinicians and healthcare leaders who are developing multi-disciplinary consult services for children with complex care needs, especially those with sepsis and MODS-associated immune dysregulation.
Objective: Re-hospitalization after sepsis can lead to impaired quality of life. Predictors of re-hospitalization could help identify sepsis survivors who may benefit from targeted interventions. Our goal was to determine whether low heart rate variability (HRV), a measure of autonomic nervous system dysfunction, is associated with re-hospitalization in pediatric septic shock survivors.Materials and Methods: This was a retrospective, observational cohort study of patients admitted between 6/2012 and 10/2020 at a single institution. Patients admitted to the pediatric intensive care unit with septic shock who had continuous heart rate data available from the bedside monitors and survived their hospitalization were included. HRV was measured using age-normalized z-scores of the integer HRV (HRVi), which is the standard deviation of the heart rate sampled every 1 s over 5 consecutive minutes. The 24-h median HRVi was assessed on two different days: the last 24 h of PICU admission (“last HRVi”) and the 24-h period with the lowest median HRVi (“lowest HRVi”). The change between the lowest and last HRVi was termed “delta HRVi.” The primary outcome was re-hospitalization within 1 year of discharge, including both emergency department encounters and hospital readmission, with sensitivity analyses at 30 and 90 days. Kruskal-Wallis, logistic regression, and Poisson regression evaluated the association between HRVi and re-hospitalizations and adjusted for potential confounders.Results: Of the 463 patients who met inclusion criteria, 306 (66%) were re-hospitalized, including 270 readmissions (58%). The last HRVi was significantly lower among re-hospitalized patients compared to those who were not (p = 0.02). There was no difference in the lowest HRVi, but patients who were re-hospitalized showed a smaller recovery in their delta HRVi compared to those who were not re-hospitalized (p = 0.02). This association remained significant after adjusting for potential confounders. In the sensitivity analysis, a smaller recovery in delta HRVi was consistently associated with a higher likelihood of re-hospitalization.Conclusion: In pediatric septic shock survivors, a smaller recovery in HRV during the index admission is significantly associated with re-hospitalization. This continuous physiologic measure could potentially be used as a predictor of patients at risk for re-hospitalization and lower health-related quality of life.
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